Hybrid nanovaccine for the co-delivery of the mRNA antigen and adjuvant

Yang, Jingnan; Arya, Smriti; Lung, Pingsai; Lin, Qiubin; Huang, Jian‐Dong; Li, Quan

doi:10.1039/c9nr05475h

Cited by 53 publications

(48 citation statements)

References 29 publications

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“…[23][24][25][26] Up to now, a variety of carriers have been investigated for the co-delivery of drugs and genes/photosensitizers in anti-cancer trails, including cationic polymers, liposomes, human serum albumin, hydrogels and inorganic nanoparticles. [27][28][29][30][31][32][33] Among them, polymeric micelles formed by amphiphilic block copolymers have gained more attention due to their unique properties such as the core/shell structure, excellent stability, and ideal encapsulation and delivery efficiency of hydrophobic drugs. [34][35][36][37] Polyethylene glycol-polylactic acid (PEG-PLA), one of the most prominent amphiphilic block copolymers, can self-assemble into micelles with core/shell structure in aqueous phase.…”

Section: Introductionmentioning

confidence: 99%

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Liang¹,

Wang²,

Shi³

et al. 2021

IJN

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Background: Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect. Materials and Methods: The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. The therapeutic efficacy and related mechanism of micelles were explored based on the in vitro and in vivo active targeting ability and the suppression of MDR, using hepatocellular carcinoma cell line HepG2 as a model. Results:The micelle was demonstrated to possess favorable cellular uptake and tumor penetration ability by specifically recognizing the nucleolin in an AS1411 aptamerdependent manner. Further, the intracellular accumulation of doxorubicin was significantly improved due to the suppression of ABCG2-mediated drug efflux by miR-519c, resulting in the efficient inhibition of tumor growth. Conclusion:The micelle-mediated co-delivery of doxorubicin and miR-519c provided a promising strategy to obtain ideal anti-cancer efficacy through the active targeting function and the reversion of MDR.

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Section: Introductionmentioning

confidence: 99%

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Liang¹,

Wang²,

Shi³

et al. 2021

IJN

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“…Moreover, due to the well-established tumor-speci c immune memory by DDP NP DOX&R848 , the rechallenged tumors were also obviously inhibited. Therefore, this work has demonstrated the robust effect of DDP BMDCs and BMDMs were prepared as previously described [43][44][45]. Brie y, bone marrow cells collected from marrow cavities of tibias of C57BL/6 mice (6-8 weeks) were cultured in culture dishes containing 10 mL RPMI 1640 medium containing streptomycin (100 mg mL − 1 ), penicillin (100 IU•mL − 1 ), and 10%…”

Section: Discussionmentioning

confidence: 99%

Hyaluronate-based Self-stabilized Nanoparticles for Reverting Immunosuppression and Immunochemotherapy in Osteosarcoma Treatment 

Zhang¹,

Yuan²,

Li³

et al. 2020

Preprint

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Background: Chemotherapy and immunotherapy are the mainly non-surgical treatment for osteosarcoma in clinic presently. However, serious side effects, short blood circulation time, and immunosuppressive tumor microenvironment have extremely limited their application. To generate an onsite combined chemotherapy and immunotherapy regimen, we designed a self-stabilized hyaluronic acid (HA) nanoparticle for the tumor-targeting delivery of doxorubicin (DOX), cisplatin (DDP), and resiquimod (R848) in osteosarcoma treatment, referred to as DDPNPDOX&R848. Methods: Here, we tested the physicochemical properties of and the ability of DDPNPDOX&R848 to induce immunogenic cell death (ICD) and revert immunosuppressive cells were characterized in vitro. The therapeutic efficacy of DDPNPDOX&R848 in vivo was evaluated in an orthotopic osteosarcoma mouse model. Furthermore, we also verified the immune memory evoking effect of DDPNPDOX&R848 in an osteosarcoma rechanllenge mouse model.Results: DDPNPDOX&R848 possesses a uniform size (similar to 190 nm) and ideal pH responsibility, and its ability to induce ICD and modulate immune cells was also proven. In vivo, regardless of the mouse model used (i.e., orthotopic osteosarcoma or rechanllenge xenografted osteosarcoma), DDPNPDOX&R848 showed significantly enhanced tumor inhibition and prolonged survival. Evoked tumoricidal immune memory responses were also demonstrated in the rechanllenged osteosarcoma mouse model.Conclusion: In summary, this intelligent codelivery platform might be a competitive candidate for osteosarcoma immunochemotherapy.

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“…Gardiquimod, a hydrophobic TLR7 adjuvant, was encapsulated into PLGA core and positive antigen‐coding mRNA was allowed to conjugate with the lipid shell. [ 66 ] Codelivery of mRNA and gardiquimod via the core/shell NPs carrier led to the effective antigen expression, DC maturation, and tumor growth inhibition. Besides, gel materials were widely applied for antigen delivery because of their biocompatibility and superior capacity in encapsulating cargos into one system.…”

Section: Nanovaccine‐based Strategies To Overcome Ldimp Cascadementioning

confidence: 99%

Nanovaccine‐Based Strategies to Overcome Challenges in the Whole Vaccination Cascade for Tumor Immunotherapy

Zhang

Zhou

et al. 2021

Small

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for their work on immune checkpoint inhibitors. Ideally, vaccination is the best strategy for tumor eradication as it can both suppress primary tumor and prevent tumor relapse and metastasis by inducing a long-term anti-cancer immune response. [3] In addition to peptide-based, [4] whole tumor cell or lysate-derived tumor vaccines, [5] development in tumor-specific mutated antigenic epitopes identification by next-generation sequencing (NGS) [6] rendered diversified tumor vaccine platforms, including neoantigen-derived peptides vaccination, whole or partial protein-encoding RNA [7] or DNA vaccines, or neoantigen-peptides-encoding recombinant viral or bacterial vectors. [8] Despite many advantages of cancer vaccines, scientists face many hurdles in translating these vaccines into the clinic. In addition to tumor immunosuppression, [9] poor immune response due to ineffective activation of antigen presenting cells (APCs), [3,10] such as dendritic cells (DCs), which are involved in the activation of T cells, [11] results in the failure of cancer vaccines. In the peripheral tissues, DCs capture antigens, migrate to lymph nodes (LNs), and finally launch an immune response. [12] Importantly, LNs contain abundant resident DCs, particularly cluster of differentiation 8 + (CD8 + ) subsets that cross-present tumor antigens. [13] Hence, LNs are the ideal targets for tumor vaccines. [14] However, subunit vaccines, composed of tumor-associated antigens (TAAs) and adjuvant, have failed to yield sufficient clinical outcomes, mainly due to inefficient vaccine delivery into DCs. [10] Though the adoptive transfer of ex vivo patient-derived DCs, equipped with tumor antigens and immune modulators, possibly overcome this challenge, [15] the labor-intensive and time-consuming ex vivo DC culturing, and variable therapeutic effects observed in the different patients having differing immune exhaustion levels impede its clinical use. [11c] To enhance vaccine delivery to DCs, scientists have made numerous efforts to utilize nanotechnology in cancer vaccine development. [16] Nanovaccines are nanoparticle-based vaccines and have shown promise in numerous preclinical researches.Nanovaccine-based immunotherapy (NBI) has received greater attention recently for its potential to prime tumor-specific immunity and establish a long-term immune memory that prevents tumor recurrence. Despite encouraging results in the recent studies, there are still numerous challenges to be tackled for eliciting potent antitumor immunity using NBI strategies. Based on the principles that govern immune response, here it is proposed that these challenges need to be addressed at the five critical cascading events: Loading tumor-specific antigens by nanoscale drug delivery systems (L); Draining tumor antigens to lymph nodes (D); Internalization by dendritic cells (DCs) (I); Maturation of DCs by costimulatory signaling (M); and Presenting tumor-peptide-major histocompatibility complexes to T cells (P) (LDIMP cascade in short). This review provides a detailed and object...

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Hybrid nanovaccine for the co-delivery of the mRNA antigen and adjuvant

Abstract: For efficient cancer vaccines, the antitumor function largely relies on cytotoxic T cells, whose activation can be effectively induced via antigen-encoding mRNA, making mRNA-based cancer vaccines an attractive approach for personalized cancer therapy.

Cited by 53 publications

References 29 publications

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Hyaluronate-based Self-stabilized Nanoparticles for Reverting Immunosuppression and Immunochemotherapy in Osteosarcoma Treatment

Nanovaccine‐Based Strategies to Overcome Challenges in the Whole Vaccination Cascade for Tumor Immunotherapy

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Hybrid nanovaccine for the co-delivery of the mRNA antigen and adjuvant

Abstract: For efficient cancer vaccines, the antitumor function largely relies on cytotoxic T cells, whose activation can be effectively induced via antigen-encoding mRNA, making mRNA-based cancer vaccines an attractive approach for personalized cancer therapy.

Cited by 53 publications

References 29 publications

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Hyaluronate-based Self-stabilized Nanoparticles for Reverting Immunosuppression and Immunochemotherapy in Osteosarcoma Treatment&nbsp;

Nanovaccine‐Based Strategies to Overcome Challenges in the Whole Vaccination Cascade for Tumor Immunotherapy

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Hyaluronate-based Self-stabilized Nanoparticles for Reverting Immunosuppression and Immunochemotherapy in Osteosarcoma Treatment